The major aim of this research is to define antigens associated with human adenocarcinoma of the pancreas with monoclonal antibody and to use these reagents as immunological probes for the development of new approaches that may prove useful for the diagnosis and treatment of pancreatic cancer. The specific aims designed to achieve this objective are: (1)\to develop murine monoclonal antibodies to pancreatic carcinoma-associated antigens; (2)\to identify monoclonal antibodies directed preferentially against such antigens by reacting hybridoma supernatants with (a)\cultured cell lines derived from metastatic and primary lesions of pancreatic carcinoma, (b)\cell lines derived from a variety of other neoplasms, (c)\cultured human lymphoblastoid cells and (d)\freshly explanted neonatal pancreatic tissues; (3)\to establish some of the immunochemical and molecular characteristics of molecules bearing antigenic determinants recognized by the monoclonal antibodies; and (4)\to critically evaluate in an animal model system in athymic (nu/nu) mice the effect of specific monoclonal antibodies on immune killing and growth characteristics of pancreatic carcinoma cells. In this regard, attempts will be made to detect tumor markers in the circulation of nude mice bearing human pancreatic tumors and to correlate their presence with tumor volume. In the past year, we have developed a panel of about 20 monoclonal antibodies, from mice immunized with either a pancreatic tumor cell line, PANC-1, or minced pancreatic carcinoma tissue metastatic to the liver. In screenings by immunoperoxidase staining of frozen tissue sections, some antibodies cross-react with normal tissues, while a few limit their reactivities to pancreatic cancer tissue. However, a dichotomy was observed between reactivities with pancreatic culture cell lines and freshly explanted pancreatic cancer tissues, indicating either antigenic loss in culture or an intrinsic underlying antigenic heterogeneity in pancreatic cancer. Molecular characterization will hopefully help in understanding the nature of tissue distribution and the possible clinical usefulness of reactive antigens.